The Frailty Syndrome: An Emergent Property of Parallel Dysregulation in Multiple Physiological Systems?

Abstract Despite its widespread presence in older adults, frailty etiology is still unclear, being associated with dysregulation in diverse physiological systems. Here, we show evidence that frailty emerges from broad loss of homeostasis integrated through complex systems dynamics. Using the NuAge and WHAS cohorts, we calculated Mahalanobis distance-based physiological dysregulation in six systems and tested the breadth, diffuseness, and nonlinearity of associations between frailty and system-specific dysregulation. We found clear support for breadth of associations, but only partial support for diffuseness and nonlinearity: 1) physiological dysregulation is positively associated with frailty in many or all systems, depending on analyses; 2) the number of dysregulated systems or the total amount of dysregulation are more predictive than individual systems, but results only partially replicated across cohorts; 3) dysregulation trends are exponential, but not always significant. These results suggest, but do not fully prove, that frailty is an emergent property of complex systems dynamics.

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The frailty syndrome as an emergent state of parallel dysregulation in multiple physiological systems

10.1101/2020.07.22.214718 ◽

2020 ◽

Author(s):

Ahmed Ghachem ◽

Linda P. Fried ◽

Véronique Legault ◽

Karen Bandeen-Roche ◽

Nancy Presse ◽

...

Keyword(s):

Older Adults ◽

Complex Systems ◽

Clinical Syndrome ◽

Emergent Property ◽

Systems Dynamics ◽

Partial Support ◽

Physiological Dysregulation ◽

Wide Range ◽

Distance Approach ◽

Physiological Systems

AbstractFrailty is a clinical syndrome often present in older adults and characterized by a heightened vulnerability to stressors. The biological antecedents and etiology of frailty are unclear despite decades of research: frailty is associated with dysregulation in a wide range of physiological systems, but no specific cause has been identified. Here, we test predictions stemming from the hypothesis that there is no specific cause: that frailty is an emergent property arising from the complex systems dynamics of the broad loss of organismal homeostasis. Specifically, we use dysregulation of six physiological systems using the Mahalanobis distance approach in two cohorts of older adults to test the breadth, diffuseness, and nonlinearity of associations between frailty and system-specific dysregulation. We find clear support for the breadth of associations between frailty and physiological dysregulation: positive associations of all systems with frailty in at least some analyses. We find partial support for diffuseness: the number of systems or total amount of dysregulation is more important than the identity of the systems dysregulated, but results only partially replicate across cohorts. We find partial support for nonlinearity: trends are exponential but not always significantly so, and power is limited for groups with very high levels of dysregulation. Overall, results are consistent with – but not definitive proof of – frailty as an emergent property of complex systems dynamics. Substantial work remains to understand how frailty relates to underlying physiological dynamics across systems.

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Effects of Sex and Physical Activity Level on Serum Biomarker-Based Physiological Dysregulation: The Impact to Predict Frailty and Mortality in the Quebec NuAge Cohort

Gerontology ◽

10.1159/000514169 ◽

2021 ◽

pp. 1-14

Author(s):

Ahmed Ghachem ◽

Frédérik Dufour ◽

Tamas Fülöp ◽

Pierrette Gaudreau ◽

Alan A. Cohen

Keyword(s):

Physical Activity ◽

Older Adults ◽

Kidney Function ◽

Oxygen Transport ◽

Physical Activity Level ◽

Rate Of Change ◽

Activity Level ◽

Men And Women ◽

Physiological Dysregulation ◽

The Impact

Background: Age-related changes in biological processes such as physiological dysregulation (the progressive loss of homeostatic capacity) vary considerably among older adults and may influence health profiles in late life. These differences could be related, at least in part, to the impact of intrinsic and extrinsic factors such as sex and physical activity level (PAL). Objectives: The objectives of this study were (1) to assess the magnitude and rate of changes in physiological dysregulation in men and women according to PAL and (2) to determine whether/how sex and PAL mediate the apparent influence of physiological dysregulation on health outcomes (frailty and mortality). Methods: We used data on 1,754 community-dwelling older adults (age = 74.4 ± 4.2 years; women = 52.4%) of the Quebec NuAge cohort study. Physiological dysregulation was calculated based on Mahalanobis distance of 31 biomarkers regrouped into 5 systems: oxygen transport, liver/kidney function, leukopoiesis, micronutrients, and lipids. Results: As expected, mean physiological dysregulation significantly increased with age while PAL decreased. For the same age and PAL, men showed higher levels of physiological dysregulation globally in 3 systems: oxygen transport, liver/kidney function, and leukopoiesis. Men also showed faster global physiological dysregulation in the liver/kidney and leukopoiesis systems. Overall, high PAL was associated with lower level and slower rate of change of physiological dysregulation. Finally, while mortality and frailty risk significantly increased with physiological dysregulation, there was no evidence for differences in these effects between sexes and PAL. Conclusion: Our results showed that both sex and PAL have a significant effect on physiological dysregulation levels and rates of change. Also, although a higher PAL was associated with lower level and slower rate of change of physiological dysregulation, there was no evidence that PAL attenuates the effect of physiological dysregulation on subsequent declines in health at the end of life. Substantial work remains to understand how modifiable behaviors impact the relationship between physiological dysregulation, frailty, and mortality in men and women.

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A physical resilience conceptual model – contributions to gerontological nursing

Revista Brasileira de Enfermagem ◽

10.1590/0034-7167-2017-0111 ◽

2018 ◽

Vol 71 (5) ◽

pp. 2589-2593 ◽

Cited By ~ 1

Author(s):

Rafael Bernardes ◽

Cristina Lavareda Baixinho

Keyword(s):

Older Adults ◽

Conceptual Model ◽

Nursing Care ◽

Functional Capacity ◽

Geriatric Nursing ◽

Frailty Syndrome ◽

Gerontological Nursing ◽

Innate Capacity ◽

Potential Applicability ◽

Definition Of

ABSTRACT Objectives: To analyze and reflect on the potential applicability of the contribution of the physical resilience conceptual model of Whitson et al. in the care for older adults. Method: The present article of reflection was structured based on the consultation of articles and definition of inherent concepts, with analysis and reason of the potentialities of its application in geriatric nursing care. Results: Physical resilience is influenced by diverse stimuli. The identification of stressors and early intervention enable the delay of the functional capacity decline. In practice, the planning of interventions that depend on the innate capacity of older adults is of utmost importance. Conclusion: The trajectory outlined over a debilitating event is relevant to understand the factors that contribute to the development of frailty or pre-frailty conditions. This knowledge allows nurses to adjust their practice and contribute to the effectiveness of interventions and a better prevention of the frailty syndrome.

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Utility of a Computerised Cognitive Screen in MCI and Depression in an Older Population

Australian Journal of Rehabilitation Counselling ◽

10.1375/jrc.16.1.14 ◽

2010 ◽

Vol 16 (1) ◽

pp. 14-26 ◽

Cited By ~ 6

Author(s):

Rachell Kingsbury ◽

Nancy A. Pachana ◽

Michael Humphreys ◽

Gerry Tehan ◽

Gerard J.A. Byrne

Keyword(s):

Older Adults ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Operating Characteristic ◽

Memory Loss ◽

Partial Support ◽

Community Based ◽

Symptoms Of Depression ◽

Clinically Significant ◽

Cognitive Screen

AbstractThe current study investigated the ability of CogniScreen to differentiate older adults with mild cognitive impairment (MCI) from those reporting symptoms of depression. Participants included 140 community-based adults (30 MCI, 15 self-rated depressed, and 95 typical older adults) aged 50–89 years. Intergroup comparisons performed using receiver operating characteristic (ROC) analyses suggest tasks within CogniScreen are sensitive to clinically significant memory loss. Data provided partial support for some CogniScreen tasks to also differentiate individuals with MCI from those who are depressed. Results suggest CogniScreen may be potentially useful in screening older adults for early cognitive decline.

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Effect of Physical Therapy on Fall-Risk and Physical Status in Older Adults with Frailty and Metabolic Syndrome

Ukraïnsʹkij žurnal medicini bìologìï ta sportu ◽

10.26693/jmbs05.06.282 ◽

2020 ◽

Vol 5 (6) ◽

pp. 282-291

Author(s):

N. P. Koval ◽

◽

M. G. Aravitska

Keyword(s):

Physical Activity ◽

Older Adults ◽

Metabolic Syndrome ◽

Physical Therapy ◽

Therapeutic Alliance ◽

Fall Risk ◽

Physical Therapist ◽

Main Group ◽

Frailty Syndrome ◽

Physical Status

The constant increase in the proportion of the disabled or partially disabled elderly population and, accordingly, patients of this age contingent, leads to the need for rehabilitation and physical therapy of persons with geriatric syndromes and various comorbid pathologies. The purpose of the study was to determine the effectiveness of a physical therapy program based on the dynamics of indicators of the fall-risk and physical status in older adults with frailty syndrome and metabolic syndrome. Material and methods. 96 older adults were examined. The control group consisted of persons without metabolic syndrome and without frailty syndrome. The main group 1 consisted of persons with metabolic syndrome and frailty syndrome who did not express a desire to cooperate with a physical therapist and / or actively improve their health on their own (low level of therapeutic alliance). They were provided with recommendations on the WHO CINDI program (diet modification, extension of household and training physical activity). Main group 2 included patients who showed consent to take active steps to improve their own health under the supervision of a physical therapist (high level of therapeutic alliance). We developed a physical therapy program for them using kinesitherapy, massage, nutritional correction, education of the patient and his family, elements of cognitive training and occupational therapy for one year. The dynamics of the state was assessed according to the results of the Short Physical Performance Battery, hand dynamometry, Senior Fitness Test, the Berg Balance Scale. Results and discussion. Older adults with metabolic syndrome and frailty syndrome demonstrated a high fall-risk (according to the results of a Short battery of physical activity tests and the Berg scale) and a statistically significant lag in physical status parameters (coordination, balance, strength, flexibility, endurance, agility) according to the parameters of the Senior Fitness Test, hand dynamometry, Short battery of physical activity tests) from their peers. These results increase the risk of adverse health effects, loss of autonomy and death. The use of physical therapy in main group 1 subjects led to a statistically significant (р<0.05) improvement in physical qualities, a decrease in the intensity of frailty signs; leveling the fall-risk in them. The low level of therapeutic alliance of persons in the main group 2 led to unsatisfactory fulfillment or non-fulfillment of the recommendations provided and is associated with a lack of improvement in their physical status and a high fall-risk. Conclusion. It is advisable to include physical therapy means in the rehabilitation programs for elderly patients with comorbid pathology of frailty and metabolic syndrome

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Exploring Early Detection of Frailty Syndrome in Older Adults: Evaluation of Oxi-Immune Markers, Clinical Parameters and Modifiable Risk Factors

Antioxidants ◽

10.3390/antiox10121975 ◽

2021 ◽

Vol 10 (12) ◽

pp. 1975

Author(s):

Armanda Teixeira-Gomes ◽

Blanca Laffon ◽

Vanessa Valdiglesias ◽

Johanna M. Gostner ◽

Thomas Felder ◽

...

Keyword(s):

Older Adults ◽

Immune Activation ◽

Future Research ◽

Clinical Parameters ◽

Frailty Syndrome ◽

Immune Markers ◽

Frailty Phenotype ◽

Age Related ◽

Inflammatory Molecules ◽

The Relationship

Ageing is accompanied with a decline in several physiological systems. Frailty is an age-related syndrome correlated to the loss of homeostasis and increased vulnerability to stressors, which is associated with increase in the risk of disability, comorbidity, hospitalisation, and death in older adults. The aim of this study was to understand the relationship between frailty syndrome, immune activation, and oxidative stress. Serum concentrations of vitamins A and E were also evaluated, as well as inflammatory biomarkers (CRP and IL-6) and oxidative DNA levels. A group of Portuguese older adults (≥65 years old) was engaged in this study and classified according to Fried’s frailty phenotype. Significant increases in the inflammatory mediators (CRP and IL-6), neopterin levels, kynurenine to tryptophan ratio (Kyn/Trp), and phenylalanine to tyrosine ratio (Phe/Tyr), and significant decreases in Trp and Tyr concentrations were observed in the presence of frailty. IL-6, neopterin, and Kyn/Trp showed potential as predictable biomarkers of frailty syndrome. Several clinical parameters such as nutrition, dependency scales, and polypharmacy were related to frailty and, consequently, may influence the associations observed. Results obtained show a progressive immune activation and production of pro-inflammatory molecules in the presence of frailty, agreeing with the inflammageing model. Future research should include different dimensions of frailty, including psychological, social, biological, and environmental factors.

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Prevalence of frailty syndrome and its associated factors among community-dwelling elderly in East Coast of Peninsular Malaysia

SAGE Open Medicine ◽

10.1177/2050312118775581 ◽

2018 ◽

Vol 6 ◽

pp. 205031211877558 ◽

Cited By ~ 10

Author(s):

Fairus Asma Mohd Hamidin ◽

Siti Nur’Asyura Adznam ◽

Zuriati Ibrahim ◽

Yoke Mun Chan ◽

Nur Hafizah Abdul Aziz

Keyword(s):

Older Adults ◽

Binary Logistic Regression ◽

Peninsular Malaysia ◽

Clinical Syndrome ◽

Community Dwelling ◽

Frailty Syndrome ◽

Increased Risk ◽

Health Related ◽

Prevention Programmes ◽

Community Dwelling Older Adults

Objective: Frailty is a clinical syndrome with increased risk of poor health outcomes and particularly prevalent in older adults and community population. The study’s aim was therefore to determine the prevalence of frailty and its association with sociodemographic and socioeconomic characteristics, health-related status, and anthropometric measurements among community-dwelling older adults. Methods: A total of 279 older adults aged 60 years and above were randomly selected. Respondents were classified as non-frail (<2 criteria) or frail (≥3 criteria) based on the ‘phenotype of frailty’. A binary logistic regression was used to determine predictors of frailty. Results: The prevalence of frailty was 18.3%. The frail older adults were positively associated with advanced age, being unmarried, hospitalisation in the previous year, poor self-rated health, and lower body mass index. Discussion: These results give an overview on underlying effects and guiding actions for prevention programmes functioning to reverse and minimise the adverse effects of frailty syndrome.

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Factors associated with frailty in older adults

Revista de Saúde Pública ◽

10.11606/s1518-8787.2018052000497 ◽

2018 ◽

Vol 52 ◽

pp. 74 ◽

Cited By ~ 7

Author(s):

Jack Roberto Silva Fhon ◽

Rosalina Aparecida Partezani Rodrigues ◽

Jair Lício Ferreira Santos ◽

Marina Aleixo Diniz ◽

Emanuella Barros dos Santos ◽

...

Keyword(s):

Older Adults ◽

Data Collection ◽

Functional Capacity ◽

Generalized Estimating Equations ◽

Estimating Equations ◽

Functional Independence ◽

Wilcoxon Test ◽

Frailty Syndrome ◽

Older Individuals ◽

Generalized Estimating

OBJECTIVE: To determine the demographic and health factors related to the frailty syndrome in older adults. METHODS: This is a longitudinal quantitative study carried out with 262 older adults aged 65 years and older, of both sexes, living at home. Data collection was carried out in Period 1 between October 2007 and February 2008, and in Period 2 between July and December 2013. For data collection, we used the sociodemographic profile instrument, the Edmonton Frail Scale, the Mini-Mental State Examination, the number of falls in the last 12 months, the number of self-reported diseases and used drugs, the Functional Independence Measure, and the Lawton and Brody Scale. We used descriptive statistics for data analysis, in the comparison of the means between periods, the nonparametric Wilcoxon test, and the method of Generalized Estimating Equations, which is considered an extension of the Generalized Linear Models with p ≤ 0.05. RESULTS: Of the 515 participants, 262 completed the follow-up, with a predominance of females, older individuals, and those who had no partner; there was an increase in frail older adults. In the Generalized Estimating Equations analysis, frailty score was related to sociodemographic (increase in age, no partner, and low education level) and health variables (more diseases, drugs, falls, and decrease in functional capacity). There was an association between the variables of age (older), marital status (no partner), and loss of functional capacity. CONCLUSIONS: Frailty syndrome was associated with increasing age, having no partner, and decreased functional capacity over time, and investments are required to prevent this syndrome and promote quality in aging.

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